ABCB1 p.Glu506Gln
| Predicted by SNAP2: | A: N (87%), C: N (66%), D: N (93%), F: D (53%), G: N (57%), H: N (66%), I: N (66%), K: N (61%), L: N (66%), M: N (97%), N: N (72%), P: D (66%), Q: N (97%), R: N (53%), S: N (72%), T: N (78%), V: N (72%), W: D (59%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Investigating the dynamic nature of the ABC transp... Biochem Soc Trans. 2015 Oct 1;43(5):1023-32. doi: 10.1042/BST20150138. Stockner T, Mullen A, MacMillan F
Investigating the dynamic nature of the ABC transporters: ABCB1 and MsbA as examples for the potential synergies of MD theory and EPR applications.
Biochem Soc Trans. 2015 Oct 1;43(5):1023-32. doi: 10.1042/BST20150138., [PMID:26517918]
Abstract [show]
ABC transporters are primary active transporters found in all kingdoms of life. Human multidrug resistance transporter ABCB1, or P-glycoprotein, has an extremely broad substrate spectrum and confers resistance against chemotherapy drug treatment in cancer cells. The bacterial ABC transporter MsbA is a lipid A flippase and a homolog to the human ABCB1 transporter, with which it partially shares its substrate spectrum. Crystal structures of MsbA and ABCB1 have been solved in multiple conformations, providing a glimpse into the possible conformational changes the transporter could be going through during the transport cycle. Crystal structures are inherently static, while a dynamic picture of the transporter in motion is needed for a complete understanding of transporter function. Molecular dynamics (MD) simulations and electron paramagnetic resonance (EPR) spectroscopy can provide structural information on ABC transporters, but the strength of these two methods lies in the potential to characterise the dynamic regime of these transporters. Information from the two methods is quite complementary. MD simulations provide an all atom dynamic picture of the time evolution of the molecular system, though with a narrow time window. EPR spectroscopy can probe structural, environmental and dynamic properties of the transporter in several time regimes, but only through the attachment sites of an exogenous spin label. In this review the synergistic effects that can be achieved by combining the two methods are highlighted, and a brief methodological background is also presented.
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No. Sentence Comment
165 Mutation of the H-loop histidine H537A and especially the catalytic E506Q strongly reduced ATP hydrolysis rates and strongly reduced transporter function, while the binding affinity of ATP and analogs remained almost unchanged [68].
X
ABCB1 p.Glu506Gln 26517918:165:68
status: NEW